Scientists start to unpick narcolepsy link to flu vaccine

LONDON (Reuters) - Scientists have found that the sleep
disorder narcolepsy can sometimes be triggered by a scientific
phenomenon known as "molecular mimicry," offering a possible
explanation for its link to a GlaxoSmithKline H1N1 pandemic flu
vaccine.

Results from U.S. researchers showed the debilitating
disorder, characterized by sudden sleepiness and muscle
weakness, can be set off by an immune response to a portion of a
protein from the H1N1 virus that is very similar to a region of
a protein called hypocretin, which is key to narcolepsy.

This can happen in genetically susceptible people, the
researchers said, adding that around 20 percent of the European
population have the genetic profile making them vulnerable.

Previous studies in countries where GSK's Pandemrix vaccine
was used in the 2009/2010 flu pandemic have found its use was
linked to a significant rise in cases of narcolepsy in children.

Studies in Britain, Finland, Sweden and Ireland found such a
link, and GSK says at least 900 narcolepsy cases associated with
the vaccine have so far been reported in Europe.

Narcolepsy is thought to be brought about by loss of
function in "wakefulness" cells called hypocretin cells in one
of the brain's sleep centers.

CROSS-REACTIVITY

Emmanuel Mignot, a narcolepsy researcher and director of the
Stanford Center for Sleep Sciences and Medicine who has been
funded by GSK to look deeper into the link, said the
relationship between H1N1 infection, vaccination and narcolepsy
gave his team "some very interesting insight into possible
causes of the condition."

In particular, he said, it strongly suggested that the
defenses, or T cells, of the immune system primed to attack H1N1
can occasionally also cross-react with hypocretin and somehow
cause the destruction of brain cells that produce hypocretin.

"When we saw that the portion of the hypocretin that seemed
to be recognized by the immune system in narcolepsy patients was
similar to a part of the pandemic 2009 H1N1 influenza
hemagglutinin molecule, we were very hopeful that we were on the
right track," said Mignot's co-researcher Elizabeth Mellins,
also at the Stanford University School of Medicine.

The Pandemrix vaccine mixed portions of viral proteins with
a non-viral "adjuvant," or booster, designed to induce a
stronger immune response. The shot was never used in the United
States and has been withdrawn from use in Europe since the links
to narcolepsy emerged.

The researchers said their study provided compelling
evidence of "molecular mimicry" - the idea that because of a
similarity between a pathogen protein and a human protein, the
normal immune response to a pathogen, such as H1N1 flu, could in
some people go awry, triggering the immune system to mistakenly
attack healthy components of the body.

Mignot said the findings, published in the journal Science
Translational Medicine, could pave the way to a new blood test
to diagnose narcolepsy.

They also point toward potential new ways to try to
intervene in narcolepsy before the specialized brain cells have
been destroyed and led to the worst level of symptoms.

"This study will shape the next decade of research into
narcolepsy," Mellins said.

Mignot, Mellins and their team now plan to study how T cell
cross-reactivity to hypocretin can destroy the hypocretin cells
in the brain, and whether this process could potentially be
blocked to potentially prevent narcolepsy.